TW541182B - Skin conditioning compositions containing an acid and a retinoid - Google Patents

Abstract

Oleanolic acid and/or ursolic acid in combination with retinol or retinyl ester substantially inhibits keratinocyte differentiation. The effects of oleanolic acid and/or ursolic acid in combination with retinol or retinyl ester are analogous to treatment with retinoic acid.

Description

541182 A7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (2 additive addition inhibition, oleanolic acid and / or ursolic acid combined with retinol or reticulum, similar effects In terms of the effect of retinoid, therefore, the mixture of oleanolic acid and / or ursolic acid and retinol or retinyl ester is easier and safer than retinoid ^ part of the present invention includes a skin conditioning A composition comprising: ⑻ from about 0.001% to about 10% of a retinoid, selected from the group consisting of retinol, retinyl esters, and mixtures thereof; ⑸ from about 0.0001% to about 50%, A compound selected from the group consisting of oleanolic acid, ursolic acid, and a mixture thereof; and (c) a cosmetically acceptable vehicle. The present invention further provides a cosmetic method for conditioning the skin, including topical application: The present invention The composition is on the skin. The present invention also provides a cosmetic method for simulating the effects of vision and feet on the skin, comprising topically applying the composition of the present invention to the skin. The term in the present invention, conditioning ", Means to avoid and deal with One or more of the following conditions: dry skin, light-prone skin, wrinkled appearance, age spots, aging skin. The composition of the present invention is also useful for increasing the whitening skin of the stratum corneum, controlling sebum secretion, and generally Increasing the skin The composition can also be used to improve the skin scaly and epidermal mesenchymal sensation. Lightness and goodness Examples Examples of lack of stem a: The composition of the invention contains one selected from the group consisting of retinol, retinyl ester, and ; This composition of 0 (group of compounds as the first necessary order. -5- X 297 mm) (Please read the precautions on the back before filling this page) Qin Ding. Meeting 541182 V. Description of the invention ( 3) f Please read the notes on the back before filling out this page} The term " visional alcohol " contains 0 isomers in addition to the rest of the known species. All-trans-resinol, 13_ 顺 _ Retinol, u_cis · retin-9-cis-retinol, 3,4-didehydro-retinol; better., Trans-retinol, 1 3-cis · retinol,% cis · Retinol-Retinol; the best is all-trans-retinol because it is commercially widely available. The esters of retinol, the term "retinol," is as defined above. The retinyl esters suitable for use in the present invention are the esters of retinol, preferably the cvcw esters, most preferably &;, &Amp;, and Cu esters, because they are the most widely available commercially. Examples of retinyl esters include, but are not limited to: retinyl palmitate, formamyl retinyl ester, and acetamyl retinyl ester , Propionate retinate, butyrate retinate, pentamate retinate, isoprene retinate, hexanoate retinoate, heptenoate retinate, octanoate retinate, nonanoic acid Retinyl esters, retinyl decanone, retinyl undecanoate, retinyl laurate, retinyl tridecanoate, retinyl dodecanoate, retinyl pentaketoate, ten Retinyl heptaestate, retinyl stearate, retinyl isostearate, retinyl nonadecanate, arachidic acid retinyl ester, camellic acid retinyl ester, lantic acid retinyl ester, oleic acid Retinol vinegar, retinol, ethylene glycol retinyl ester, hydroxycaproyl retinyl ester, cinnamyl retinyl ester, tartaric acid retinyl ester. According to the report, ^ printed by the Central Consumers Bureau Consumer Cooperative ^ The preferred alcohols applicable in the present invention are selected from the group consisting of palmitate retinase, formamyl retinyl ester, and acetamidine retinyl ester because they are commercially available. Most widely available and least expensive. Retinyl lanate can also be used because it has good effects. Vision S and / or the amount of Vision Vinegar in the composition of the present invention is from about -6-This paper size is applicable to Chinese National Standard (CNS) A4 specifications (210X297 cm) 541182 A7 B7 V. Description of the invention ( 4) 0.001% to about 10%, preferably from about 0.01% to about 1%, and most preferably from about 0.01% to about 0.5%. The second essential ingredient contained in the composition of the present invention is oleanolic acid, ursolic acid and their mixtures. These acids have the following structure: printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

Ursolic acid paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page)-Binding and binding 541182 V. Description of the invention (5) It should be understood according to the combination The properties p Η > and / ν are from 2 people " 丄 different 'oleanolic acid and / or ursolic acid in the composition of the present invention may be salt ... glutamate. For example, the content of the alkali metal salt or alkaline earth metal oleanolic acid and / or ursolic acid in the composition of Tai and Ben Ao Yue is from about 0.0001% to about 50%. The range is from about 0.01% to about 10%, and the best range is from about 0.1% to about 5%. Cosmetics and cosmetics can be added to the composition of the present invention. The composition of the present invention is also innocuous. I η is a cosmetic acceptable vehicle, which is used as a diluent for the active ingredients in the composition. Therefore, when it is applied to the skin, the application of the composition can be facilitated. Other than water or vehicles other than water, liquid or solid emulsifiers' solvents, humectants, thickeners and powders can be included. Particularly preferred non-aqueous carriers are silicones suitable for use in polydimethylsiloxane and / or polyxylylsiloxane, which have a temperature of from 10 to 10,000 mm2 / s at 25 ° C. Those with viscosity, especially those who need it are mixtures of low-viscosity and high-viscosity silicones. These silicones were purchased from General Electronics, trade names VicasU and SF, and 200 and 50 series from Dow Corning. The amount of silicone used in the composition of the present invention is from about 5% to about 95% by weight of the composition, preferably from about 25% to about 90%. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page). The acceptable media for cosmetics usually account for about 5% to about 99.9% of the weight of the composition, preferably from From about 25% to about 80%, and 'to make up the amount of the composition in the absence of other modifiers. Preferably, the vehicle solution is at least 50% by weight of the composition, and most preferably at least 80% by weight of the composition. Preferably, the composition of the present invention contains at least about 50% by weight, most preferably 60 to 800 weight-8-This paper size applies to Chinese National Standard (CNS) A4 specification (210 × 297 mm) 541182 Α7 B7 5. Description of the invention (6) Amount of water. Skin gain materials and cosmetic conditioners added as needed may contain oil or oily substances to form a water-in-oil emulsion or oil-in-water emulsion together with the emulsifier, which mostly depends on the average hydrophilicity-lipophilicity of the emulsifier used Balance value (HLB). The compositions of the present invention preferably include sunscreen agents, including those commonly used to block ultraviolet rays. Exemplary compounds such as derivatives of pABA, cinnamate and salicylate, for example, octylmethoxycinnamate and 2-hydroxy-4-methoxyphenylphenol ketone (known as oxygen Acetophenone), octylmethoxycinnamate and 2-hydroxy-4-methoxyphenylphenol ketone are commercially available under the trade names Parsol MCX and Benzophenone-3, respectively. The exact amount of sunscreen used in the emulsion may vary depending on the desired degree of protection from solar suv radiation. Another preferred optional ingredient is selected from essential fatty acids (EFAs), that is, they are essential fatty acids for plasma membrane formation of all cells. When the EFA of keratinocytes is insufficient, the cells will be in a high pre-activated state. Supplying EFA can solve this problem. EFA can also enhance the phospholipid biosynthesis of epithelial cells and provide the barrier formation of lipids in epithelial cells. This essential fatty acid is preferably selected from the group consisting of lantic acid, γ-lanic acid, homophagic lantic acid, niobic acid, icos- stone trans- (η-6,9,1 3) -dihydrazone version of arachidonic acid, α_wool Acid, eicosapentapentanoic acid, hexenoic acid and mixtures thereof. There is still another preferred ingredient as needed, which is selected from the group of azoles, for example, cis-pyrrole, bispyrrole, cloth trimer pyrrole, ketoconazole, mcconsylpyrrolidone, and ekonsylpyrazole. , Intacons ρ ratio ρ, said Kang Si ρ ratio, 2-9-This paper size applies Chinese National Standard (CNS) A4 specifications (210X 297 mm) — J— I- -I mj I m · (Please read the notes on the back before filling out this page) Order printed by the Central Consumers ’Cooperative of the Ministry of Economic Affairs printed by 541182 A7 B7 Printed by the Central Consumers’ Cooperative of the Ministry of Economic Affairs printed by the Consumer Cooperative of the Ministry of Economic Affairs Oxyconsyl pyrrol, thioconsyl pyrrol, nylon consiole, and mixtures thereof. The content of pyrrole in the composition of the present invention may be from about 0.001% to about 50%, preferably from about 0.00%. 〇1% to about 10%, preferably from about 0.1% to about 5%. Emulsifiers are generally incorporated into the cosmetic composition of the present invention, and these emulsifiers can be from 0.5% to 5% by weight of the total composition 50% by weight, preferably between $% and 30% by weight. In general chemical classification, emulsifiers Classified as esters, fatty acids and alcohols, polyhydric alcohols and hydrocarbons. Esters can be mono- or di-esters, and acceptable di-esters of fatty acids include dibutyl adipate, diethyl sebacate, Diisopropyl dimer, and dioctyl succinate; acceptable branched fatty acid esters include 2-ethyl-hexyldodecane, bismuth isopropyl ester, and isostearic palmitate Fatty acid esters; acceptable tribasic acid esters include triisopropyltrilanic acid and trilauryl glutamic acid; acceptable linear fatty acid esters include lauryl palmitate and caproyl Dodecyl esters of oleyl oleate and stearic acid oleate. Preferred esters include coconut-based vinegar / octyl vinegar (a mixture of coconut-based octyl vinegar and coconut-based octyl vinegar) 'c = Alcohol ether ethyl ester, = isopropylhexanoate and hexadecyl octanone. Suitable fatty acids and alcohols include those compounds having 1G to fine carbon atoms. Among these compounds ^ 去去 # 丄1, 1 is ten 7T:!: Yuan group, dodecyl group, palmity group and stearic alcohol and acid. Polyol series, linear and branched, which can be used as emulsifier. Polyalkylene-based compound: For example, propylene glycol 'mannitol and glycerol are better, and poly & alcohols such as polypropylene glycol and polyethylene glycol. Butylene glycol and propylene glycol are suitable for this paper Guan Jiabiao (Please read the precautions on the back before filling out this page) · Install II ----------- r -10-541182 A7 B7 V. Description of the invention (8-series special good can be used as penetration accelerator Examples of hydrocarbons that can be used as emulsifiers are those having 2 to 3 c carbon atoms in their hydrocarbon chains. Specific examples include mineral oil, petroleum gum, propolis, and dissimilated ash oil. The cosmetic composition of the present invention The other functional ingredients contained in the composition are thickeners. Thickeners usually exist in the range of from 0.01% to 20% by weight of the composition, preferably from 0.5% to 10% by weight. An example of a thickener is a cross-linked polyacrylate material, available from B.F. Godddd, under the trade name Carbopol. Examples of gums that can be used include xanthan gum, gellan gum, gelatin, sycamore gum, protein and soybean gum. Under certain circumstances, thickening can be achieved by the addition of silicone or emulsifiers, such as silicone gums with a viscosity of more than 10 d Torr, and esters with dual functions such as glyceryl stearate. Powders can also be incorporated into the cosmetic composition of the present invention. These powders include scallion powder, talc, kaolin, starch, homogeneous clay, chemically modified magnesium aluminosilicate, and organically modified magnesium Supporting clay, hydrated aluminum silicate, fumed silica, aluminum starch octyl succinate, and mixtures thereof. Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Order other modifiers. The minor ingredients can also be incorporated into the cosmetic composition of the present invention. These ingredients include colorants, pearlescent Agents and perfumes, and the amount of these remaining & whole ingredients minor components may range from 0.001% to 0% by weight of the composition. Use of local and crude compounds The cosmetic composition of the present invention is mainly intended for topical application to humans -11-541182 Α7

Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs: The above products are especially intended to be used as skin care and reduce the appearance of sensitive skin or aging skin. State-Yangguang 'is to take a small amount of the composition (for example, 1 to 100 ml) from a suitable M or a device and apply it to the exposed area of the skin. The devices are all hook-coated and / or smeared on the second skin. In the form of monthly products, the topical skin treatment composition in January can be appropriately formulated into an emulsion, + or three. The composition can be packaged in an appropriate container according to the needs of the consumer and its viscosity, for example, emulsion or The cream can be packaged in a bottle or a roller ball using a spray-propulsion spray device towel, or in a container suitable for finger operation. When the composition is a cream, it can only be stored in a non-deformed bottle or squeezed. Out of the bottle, such as a test tube or capped sprayer. This composition can also be packaged in capsules such as those described in U.S. Patent No. 5,063,057. Accordingly, the present invention also provides a closed container containing a cosmetically acceptable composition as defined herein. The following specific examples further illustrate the invention. Materials and methods Cell culture lanes human keratin cells (treated with trypsin and isolated from the forehead skin of newborns) at 〇1! 丨 3 € (： 〇〇 conditioner (〇) \ 1 £) ^^ 1115 ? 12 (1: 1) medium / 10% fetal bovine plasma and cultured in the presence of irradiated mouse fibroblasts to establish individual keratinocyte replicas. -This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 × 297 mm) (Please read the precautions on the back before filling out this page} Binding 541182 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Ι〇) incubate until the second passage, and then frozen for later use. Replaced with 0 "5 mM # 5 plasma-free MCDB 153 base medium purchased from Clonetics (San Diego, CA). Keratinocyte Proliferation Medium (KGM), or 0.09 mM # 5 keratin-free cell medium (KSFM) purchased from GIBCO, first dissolve frozen second-passage keratin cells and implant into the above media, And continue to culture for 5 days. On the 7th day, when the cells have 8 After 0-9 0% confluence, they were trypsinized and implanted in plasma-free medium for many different tests. Transglutamine 醯 gfeaij was determined to be transglutamine marinated to determine the integration of C. lepidium leukocytes in epithelial cells In the final differentiation process, a 15-nm-thick protein layer (known as keratinocytes (CE)) is formed on the inner surface of the outer cell shape, and ce is composed of many different proteins. Glutamine enzymes (TGases) catalyze the formation of Nε- (γ-glutamine amino) lysine isodipeptide bonds and cross-linking bonds together. Transglutaminase 丨 0 is a rich store In the differentiated layer of epithelial cells, especially the columnar layer, it does not exist in the undifferentiated base epithelial layer. Therefore, transglutaminase I is a useful source for the differentiation of epithelial keratin cells. The TGasesj content represents more differentiation status. The ELISA-based TGases assay (using TGases I antibody) is used to analyze the differentiation status of the cultured keratin cells in the following examples. For Example 1, the following procedure was used : Put keratin cells ( Cultured in the above method) Implanted into 96 wells with a density of 3,000 cells per 200 μΐ medium per well. To be cultured for 4 days-13-This paper is in accordance with Chinese National Standard (CNS) Α4 Specifications (210X 297 meals) (Please read the precautions on the back before filling out this page} Order 541182 A7 B7 V. Invention Description (11 Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, replace the medium with a test substance (each time Six replicates of the test medium were used. After another 72 hours, the medium was aerated and the flat disks were stored at -70 ° C. Remove the plate from the freezer, wash the cells with pBS, add 100 μΐ of sterilized water, freeze the cells at -70 ° C for freeze-reconstitution, and then dissolve. Cell lines were incubated at room temperature (R / T) with pbs / 3% BSA (washing buffer, bovine blood samples) for one hour, and then washed with fresh washing buffer. The first anti-bone · ^ single replica anti-human glutamine synthetase antibody (igG) purchased from Biomedical Company and diluted with i: 2,000 washing buffer was incubated at -37 ° C for 1 hour, and then Wash twice with washing buffer. Then, 50 μΐ of secondary antibody diluted in i: 4,000 washing buffer (17 sera, peroxidase-conjugated anti-mouse mouse IgG, purchased from Amersham) was cultured at 37 ° C for 1 hour, and then Wash twice with washing buffer. Base solution (4 g of ortho-phenylenediamine and 30% of 3 3… in 10 ml of 0 ″ μ citrate buffered to pH 5.0) at room temperature (R / T) and dark The cells were cultured for 5 minutes in medium (encapsulated with aluminum pod), and the reaction was stopped after the addition of 50 μ 的 of 4N h2SO4. The absorbance of the sample was read from a flat-panel readout meter at 492 nm. In 6 replicate samples, Four were treated with two antibodies, and the other two were treated only with the second anti-osteoporosis (ie, the background of the bound enzyme conjugate Ab was determined). TGases were determined by subtracting the background correction readings from each treatment and recorded The average value sd of exposure to the two antibodies. In Example 2, the following procedure was used: Keratin cells (cultured as described above) were implanted into 96 well-shaped dishes, the density of which must be 200 per 200 There are 3,000 cells in each well of the μΐ medium. After 4 days of culture, the medium is replaced with a medium containing a test substance (6 copies for each test). -14 CNS) Α4 specification (210 × 297 public holidays) (Please read the precautions on the back before filling this page) β Γ Ρ 541182 A7 _ ___B7 V. Description of the invention (12) After another 7 2 hours, the medium is aerated and the pan is stored at -70 ° C. Remove the pan from the freezer and wash the cells with pBS 3 Add 100 μΐ of sterilized water, freeze the cells at _70 ° CT for freezing and reconstitution, and then lyse. The cell line was incubated at room temperature (R / T) with pBS / 3% BSA (/ eye wash buffer). (Blood sample) for 1 hour, and then washed with a new washing buffer. The first antibody single replica anti-human glutamine was purchased from Biomedica 1 and diluted with a washing buffer of 1: 2,000. The amylase mouse antibody (IgG) was cultured at -37 ° C for 1 hour, and then washed twice with washing buffer. Then, 50 μΐ of a second antibody (Fab residue was diluted with 1: 4,000 washing buffer) , Peroxidase-conjugated anti-mouse IgG, from Amersham) was incubated at 37 ° C for 1 hour, and then washed twice with washing buffer. The base solution (4 mg of o-phenylenediamine and 3 · 3 μ1 of 300 / 〇2〇2 in 10 ml (M μ buffered citrate to pH 5.0) at room temperature (r / butyl) and in the dark The cells were cultured for 5 minutes, and the reaction was stopped after adding 50 μ 1 of 4N ΗΘ〇4. The absorbance of the sample was read from a flat-plate reader at 492 nm. 4 were treated with two antibodies, and the other 2 were treated with only the second antibody (ie, the background of the binding enzyme conjugate Ab was determined). The measurement of transglutaminase was performed by subtracting the background correction for each treatment from the center of the Ministry of Economic Affairs Printed by the Consumer Bureau of Standards Bureau (please read the precautions on the back before filling out this page) The readings obtained are determined, and the average value of the exposure to the two antibodies is recorded. S · d · ° DNA measurement after cell processing The TGase I assay is affected by the number of cells, that is, the larger the number of cells, the greater the amount of TGase-1 measured. By normalizing the amount of TGase I in the same well to the same DNA content as the cells, -15- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 541182 A7 B7 V. Description of the invention (13) ( (Please read the notes on the back before filling out this page) to eliminate the variation caused by the number of cells. The amount of DNA is a particularly useful indicator of the number of cells, including also for keratin cells, because each cell has its own function and the same genome, so the amount of DNA can be determined. The total amount of DNA in the cell wall is directly proportional to the number of cells in the cell wall. The quantification of DNA is used to normalize the value of TGase to the number of cells. Keratin cells are implanted into 96 well-shaped dishes at a density of 3,000 cells per 200 μΐ mediated overflow wells. After 4 days of incubation, the medium was replaced with a medium containing reduced substances (6 replicates for each test). After another 72 hours, the medium was aerated and the flat disk was stored at -70. (: At least 1.5 hours. Remove the plate from the freezer and dissolve for 30 minutes. Add 100 μΐ Hoechst dye (1 μΐ / ml final concentration), then culture the cells for 15 minutes, cover and autofluorescence Read the absorbance in the meter (360 nm and 460 nm). Remove the dye solution and wash the culture wells with the PBS prepared in TGase. 1Γ Example 1 To change the meristematic state of keratin cells, compare with retic acid网 薄 # With the addition of retinoid (RA) and retinol (ROH), the effects of normalizing the amount of transglutaminase to the cell's DNA content have been tested and are listed in Table 1. Central Standards of the Ministry of Economic Affairs Bureau Consumer Consumption Cooperative Prints Proper Standards! Home Country I Country I Use-£ J Degree One Foot Sheet of Paper I

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7 B V. Description of the Invention (14) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs

CSJ CO NJ CsJ CsJ pr LH X f— '〇υτ X ι— * 〇LH X H-1 〇X > -1 〇LH X H- * 〇LH X 0 1¾ 22: 2Γ 3f 22: 2Γ knife 〇 > 73 O > 70 q > CO Ο! + Ο υτ Ό Η C0 1+ ο \ D CD Ι-τ ο UJ 0 LJ two H · 0 two ol-1 £ 〇fO Cvj 0 H * 0! -* i—1 CO AA Ι ο CO A 0 -T4 丨 + 上 how 00 CL H / · s C ') * JU- CJ hr. * ^ σ V · — 〇 c * P c * P LH c9 Cf > wb 0 〇N〇X ο ο ο Η 〇oo M 〇〇〇〇〇〇〇〇〇〇１—1 〇〇〇1 < CO-=]? ο ο ο Η ooo h-4 0 0 0 1-1 〇fO 1 〇〇〇H-1 0 0 0!-* —Ό ^ < ^ Μ Ο ίο X ο o 0 0 〇〇 一 Ό% < :: ο ο Η CD 2 1 0 0 H- * 0 0 〇〇〇〇〇1- * 73⑺ 〇IJ 丄 Οι X o 0 〇〇〇〇0 222 1 o 〇0 0 H- * 0 0 ι- * 〇Η * 0 — 〇 ΙΟ —ο. X -17- (Please read the precautions on the back before filling this page) The size of the paper used for this edition applies to the Chinese National Standard (CNS) A4 (210X297 mm) 541182 A7 B7 V. Description of the invention 15) All tested retinoic acid concentrations, ie, 2 5 χ 1〇-7 Μ, 2.5 X 1 〇-8 Μ, 2.5 χ 10 Μ, compared to the ethanol control group, reduced The meristematic effect of keratin cells, and for each relevant concentration ····· 5χ 10-7 M, 2.5 X 10 · 8 M, 2 · 5 X 10-9 M, as far as retinol treatment, its degree of improvement also increased . The reduction in transglutaminase content depends on the doses of retinoid and retinol, which is consistent with the argument that retinoid is more effective than retinol in changing the keratinocyte meristem state. Session 2

The effect of homoacid and retinoic acid on the differentiation of adult keratinocytes as normal I on TGase I normalization to cellular DNA content is related to the determination after 72 hours of treatment with test compounds. The result series are shown in Table 2. (Please read the precautions on the back before filling out this page) Order Φ Printed by the Central Consumers Bureau of the Ministry of Economic Affairs, printed by the Consumer Cooperative, the paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 541182 5. Description of the invention (17) From the data in Table 2, it can be seen that 2.5 × 1 0-7M < retinoic acid is quite effective in suppressing keratinizing TGase I content (relative to 44% of control), and 2 × χ〇_7M is more effective than sight The acid is ineffective, and oleanolic acid of 0.6 μ when used alone has no inhibitory effect on keratinized TGase I content. However, 2 · 5χι〇-7M of retinol + 6 μ < oleanolic acid inhibits keratinization TGase Γ content to a controlled amount. Therefore, oleanolic acid and retinol have similar effects on keratinocyte differentiation Additive effect of net acid effect. In Examples 1 to 2, retinoids were used as the positive control group and compared with the rest of the compound analysis 纟 reference group. Vision § cross, at a certain dose can reduce the content of transglutaminase in skin keratin cells, in other words, retinoic acid can reduce the differentiation of low keratin cells. In inhibiting the differentiation of keratin cells, retinol and retinyl palmitate are obviously less effective than retinoid. The unpredictable effect of the above example printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs is that the influence of retinol or retinol on cultured keratin cells can be greatly increased to those close to retinoid, which This is achieved by combining retinol or an ester with a compound that weighs from about 0.0001% to about 50% of the composition, wherein the compound is shown by in vitro microsomal assays at a concentration of 100%, Can inhibit at least 20% of retinal esterification reactions catalyzed by ^ RAT or ARAT. These effects are not only greater than those of retinol or its esters alone, but also greater than those of combining these two ingredients to produce an additive effect on keratin cells similar to that of retinoid. Examples 3-8 are examples of the compositions of the present invention. These compositions can be prepared according to conventional methods, which are suitable for cosmetic use. In particular, these compositions are suitable for gradation, thick seam, drying, cracking, In the use of aging or damaged skin to improve the appearance and touch of the skin, the composition of the present invention is suitable for -20- the paper rule iUiTssi home standard (CNS) 7 ^ 721GX297 mm) 541182

7 B V. Description of the invention (18) Suitable for use on healthy skin to avoid or delay aging. Example 3 This example illustrates a high internal phase water-in-oil emulsion incorporated into the composition of the present invention. (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs This example is an example of an oil-in-water cream that incorporates the composition of the present invention. % w / w Retinol 0.15 Mineral oil 4 Ursolic acid 1 Brij 561 4 Alfol 16RO1 4 Triethanolamine 0.75 -21-% w / w Retinol 0.5 Fully hydrogenated gardenia oil 3.9 Ursolic acid 5 Brij 921 5 B entone 3 8 0.5 MgS047H20 0.3 Butylated hydroxymethyl ketone 0.01 Perfume amount of water to 100 This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 1

Brij 92 series poly (ethylene oxide) olein. Example 4 541182

A B V. Description of the invention (19) 1,3-butanediol 3 Xanthan gum 0.3 Perfume Amount Butyl hydroxymethanone 0.01 Water to 100 * Brij 56 series cetyl alcohol POE (10). Alfol 16RO is cetyl alcohol. Example 5 This example illustrates the alcohol-containing emulsion of the present invention. % w / w Retinyl palmitate 0.15 Ursolic acid 0.1 Ethanol 40 Percent of butylated hydroxymethyl ketone 0.01 Water to 100 Example 6 (Please read the precautions on the back before filling this page) Employees of the Central Bureau of Standards, Ministry of Economic Affairs Printed by a cooperative This example illustrates another alcohol-containing emulsion containing a composition of the present invention. % w / w Retinol 0.15 Ursolic acid 0.1 Ethanol 40 Antioxidant 0.1 -22- This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 541182

A B Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (20) This example illustrates the sunscreen incorporated in the composition of the present invention. % w / w Retinyl palmitate 0.01 Ursolic acid 0.1 Shixiong with oil 2 0 0 cts 7.5 Glyceryl monostearate 3 Cetyl stearate 1.6 Poly (ethylene oxide)-(20)- Cetyl Alcohol 1.4 Xanthan Gum 0.5 Parsol 1789 1.5 Amyl Methoxy Succinate (Parsol MCX) 7 Perfume Moderate Pigment Moderate Water to 100 Example 8 This example illustrates a non-aqueous skin conditioning combination incorporated into the composition of the present invention Thing. % w / w retinoic acid 0.15 oleanolic acid 1 -23- (Please read the precautions on the back before filling in this page) Perfume amount of water to 100 This paper size applies Chinese National Standard (CNS) A4 specification (210X 297) %) 541182

AB 5. Description of the invention (21) Silicone glue SE-301 10 Silicone fluid 3452 20 Silicone fluid 3443 55.79 Squalin 10 Lanolin 0.01 Cholesterol 0.03 2-Hydroxy-n-octanoic acid 0.7 Vitamin E Lanolin 0.5 Grass oil 0.5 ethanol 2 dimethyl silicone polymer, which has a molecular weight of at least 50,000 and a viscosity of at least 10,000 d Torr at 25 ° C, was purchased from GEC. Dimethyxone cyclic pentamer was purchased from Dow Corning. Dimethyxene is a cyclic tetramer and was purchased from Dow C O r n i n g. ------------ ^ --- :. 11 ------ 0 (Please read the notes on the back before filling out this page) Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs- 24- This paper size applies to China National Standard (CNS) A4 (210X 297mm)

Claims (1)

541182 ABCD VI. Application for Patent Scope 1. A skin conditioning composition comprising: ⑻0.001% to 10% retinol; (b) 0.0001% to 50% selected from oleanolic acid, ursolic acid and others Acid of the mixture; and 2 (C) —a cosmetically acceptable vehicle. The composition of item 1 of the 2 color rule, wherein the composition is selected from the group consisting of dry skin, skin damaged by light exposure, wrinkles ^, X 'aging skin, facial acne skin sebaceous gland suppression > Dull skin. (Please read the notes on the back before filling in this page. ”Order ¾ Copy from the Central Ministry of Economic Affairs of the Ministry of Economic Affairs, X Consumer Cooperatives 4 Use China 25-National Standards (CNS) (210X 297 male thin) (^ --- each column is filled by this bureau) f! R; / y Revised manual (March 89) Λ4 C4 541182 Ming, invention new, name patent specification Chinese skin with acid and retinoid combination SKIN CONDITIONING COMPOSITIONS CONTAINING AN ACID AND A RETINOID Name 1. Stuart Paton Grange 2. Ian Richard Scott's invention and creation y Nationality 1. United Kingdom 2. British residence and residence 1 New Jersey, USA 181 Middlesex Street, Paramus, State 2. No. 9 Paine Road, Allendale, New Jersey, United States Name (Name) Unilever Dutch Nationality Dutch Resident, Residence (Office) Rotterdam, Netherlands City Weiner 45 No. 5 Jian Paulas Van Kitt Representative Name It is the standard of domestic valve (CNS) A4 in Qiaozhong valve (29? Male f "541182 A7 B7 Chinese Version of the Chinese Patent Application No. 861 18988 amendment page (December 90) V. Description of the invention (1) Field of the invention The present invention relates to skin conditioning compositions containing acids and retinoids, and also relates to such skin conditioning compositions. The method of applying the composition to the skin. BACKGROUND OF THE INVENTION Retinol (vitamin A) is an endogenous compound naturally produced in the human body, which is necessary for the differentiation of normal epithelial cells. Natural and synthetic vitamin A derivatives have been widely used in the treatment of many skin disorders as skin repair agents or skin regeneration agents, and retinoids have been used in the conditioning of many skin symptoms, such as ... Streaks, psoriasis, and age spots can be found in, for example, valUquist, A. et al., Published in hvew. Journal, 94th volume, published by Holland vf Content DB · and Cunliffe WJ (1990). In the literature on pages 496 to 498, "Pharmacology 〇f Retinols in skin" published by Ellis, CN ·, et al., Vasei, Karger, 3rd edition, ( 1989), pages 249 to 252; published by Lowe, NJ ·, et al., Pharmacological effects of retinol on the skin (Pharmac〇1〇gy 0: f Retinols in Skin), Vol. 3, (1989), pages 240 to 248; PCT Patent Application No. WO 93/19743. It is generally believed that retinol or esters of retinol are preferred. Retinol is an endogenous compound. Retinol esters are hydrolyzed in vivo to produce retinol. The present invention is based in part on the following findings: retinol or a blend of retinol, when combined with oleanolic acid and / or When ursolic acid is used in combination, the differentiation of keratin cells will produce -4- This paper is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm)-541182 No. 861 18988 Patent Application Chinese Manual Correction Page (December 90) A B7 V. Description of the invention (16) 2.5 X 1 ('乙 1 (0 | 1lo. * M 磺 锋 湃 黪 2.5 XK 二 2 axe -.- > 一 / lis- 2.5X 10 "M 1 (> til t 27. 61 ± 10.79 (53%) 49.2 ± 2.7G (94¾) 4G. 31 ± 5.. 31 {92S 22b ± 2.31 M2U 52.78 i 5.69 {1) uf ^ TGasc / DMAx lo'lis.d. ^ s%) 0.002 0.329 0.235 0.001 0.005 0.5G5 0.001 0.235 1 °, M 11011 I) iprvs 2.5X • Order · 0.328 0.001 ο. 001 0 .ool p ^ vs 2.5 X 10 · < Μ n > 0.002 0.55 0.001 9 This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) 0.329 p ίΛ vs 2.5 X 102